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氟伐他汀对环孢素A所致大鼠成纤维细胞肾毒性的保护作用

Protective effects of fluvastatin on cyclosporine A-induced nephrotoxicity in rat fibroblast
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摘要 目的观察免疫抑制剂环孢素A(CsA)对大鼠肾脏成纤维细胞增殖及细胞因子表达的影响以及氟伐他汀的干预作用,探讨氟伐他汀对CsA肾毒性的保护作用。方法体外培养大鼠肾脏成纤维细胞,四甲基偶氮唑盐(MTT)比色法测定CsA及氟伐他汀对细胞增殖的影响。RT—PCR方法检测转化生长因子β1(TGF—β1)、结缔组织生长因子(CTGF)及c-fns mRNA水平。Western印迹检测纤连蛋白(FN)的表达。结果CsA可明显抑制成纤维细胞增殖,且呈剂量和时间依赖效应(P〈0.05)。氟伐他汀与CsA合用后,对细胞增殖有明显的抑制作用(P〈0.01)。CsA刺激成纤维细胞TGF-β1、CTGF、c-fns及FN的产生(P〈0.05),氟伐他汀可下调这些改变(P〈0.05)。结论氟伐他汀可减轻CsA所致的大鼠肾脏成纤维细胞毒性。 Objective To investigate the protective effects of fluvastatin(Flu) on rat renal fibroblasts proliferation and cytokines expression induced by cyclosporine A (CsA). Methods The fibroblasts were cultured with CsA or with CsA plus fluvastatin. The cellular proliferation was determined by MTT colorimetry. The mRNA expression of transforming growth factor β1(TGF-β1), connetive tissue growth factor (CTGF) and c-fos was detected by RT-RCR. The protein level of fibronectin (FN) was measured by Western blotting. Results CsA inhibited the proliferation of fibroblasts in dose- and time-dependent manner (P〈0.05). Treatment with Flu accelerated the suppression of fibroblasts resulted from CsA (P〈0.01). CsA stimulated the expression of TGF-β1, CTGF, c-fos and FN compared with control group(P〈0.05), which could be down-regulated by Flu (P〈0.05). Conclusion Fluvastatin may relieve CsA-induced nephrotoxicity in rat fibroblasts.
出处 《中华肾脏病杂志》 CAS CSCD 北大核心 2008年第9期647-650,共4页 Chinese Journal of Nephrology
基金 河南省科技攻关项目(0324410084) 河南省杰出青年基金(74100510006)
关键词 环孢菌素 成纤维细胞 细胞增殖 转化生长因子B 纤连蛋 白类 氟伐他汀 Cyclosporine Fibroblasts Cell proliferation Transforming growth factor β Fibronectins Fluvastatin
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